Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis

Overview

Journal Nutrients

Date 2025 Jan 25

PMID 39861394

Authors

Erika Melendez-Oliva

Oliver Martinez-Pozas

Pierluigi Sinatti

Carmen Martin Carreras-Presas

Juan Nicolas Cuenca-Zaldivar

Silvia Turroni

Eleuterio A Sanchez Romero

Affiliations

Soon will be listed here.

Abstract

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a "wear and tear" condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA.

Materials And Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for "observational studies". The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools.

Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study confirmed the relationship between relative abundance of spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus or plasma markers of the tryptophan pathway.

Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients.

References

Hazrati E, Eftekhar S, Mosaed R, Dini S, Namazi M . Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions. Mol Pain. 2024; 20:17448069241275097. PMC: 11331475. DOI: 10.1177/17448069241275097. View

O-Sullivan I, Natarajan Anbazhagan A, Singh G, Ma K, Green S, Singhal M . Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model. Biomedicines. 2022; 10(6). PMC: 9220766. DOI: 10.3390/biomedicines10061298. View

Zhao Z, Xin F, Xue Y, Hu Z, Han Y, Ma F . Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp Mol Med. 2019; 51(9):1-14. PMC: 6802644. DOI: 10.1038/s12276-019-0304-5. View

Yadav S, Sapra L, Srivastava R . Polysaccharides to postbiotics: Nurturing bone health via modulating "gut-immune axis". Int J Biol Macromol. 2024; 278(Pt 2):134655. DOI: 10.1016/j.ijbiomac.2024.134655. View

Sanchez Romero E, Melendez Oliva E, Alonso Perez J, Martin Perez S, Turroni S, Marchese L . Relationship between the Gut Microbiome and Osteoarthritis Pain: Review of the Literature. Nutrients. 2021; 13(3). PMC: 7996179. DOI: 10.3390/nu13030716. View

Arora V, Singh G, O-Sullivan I, Ma K, Natarajan Anbazhagan A, Votta-Velis E . Gut-microbiota modulation: The impact of thegut-microbiotaon osteoarthritis. Gene. 2021; 785:145619. DOI: 10.1016/j.gene.2021.145619. View

Boer C, Radjabzadeh D, Medina-Gomez C, Garmaeva S, Schiphof D, Arp P . Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun. 2019; 10(1):4881. PMC: 6814863. DOI: 10.1038/s41467-019-12873-4. View

Leifer V, Katz J, Losina E . The burden of OA-health services and economics. Osteoarthritis Cartilage. 2021; 30(1):10-16. PMC: 8605034. DOI: 10.1016/j.joca.2021.05.007. View

Ott M, Plummer M, Roos M . How vague is vague? How informative is informative? Reference analysis for Bayesian meta-analysis. Stat Med. 2021; 40(20):4505-4521. PMC: 8453582. DOI: 10.1002/sim.9076. View

10.

Tsuji A, Ikeda Y, Yoshikawa S, Taniguchi K, Sawamura H, Morikawa S . The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases. Int J Mol Sci. 2023; 24(6). PMC: 10051340. DOI: 10.3390/ijms24065742. View

11.

Beaule P, Shea B, Abedlbary H, Ahmadzai N, Skidmore B, Mallick R . A protocol for a systematic review of the diagnostic accuracy of blood markers, synovial fluid, and tissue testing in periprosthetic joint infections (PJI). Syst Rev. 2015; 4:148. PMC: 4630899. DOI: 10.1186/s13643-015-0124-1. View

11.

Efthimiou O, Mavridis D, Debray T, Samara M, Belger M, Siontis G . Combining randomized and non-randomized evidence in network meta-analysis. Stat Med. 2017; 36(8):1210-1226. DOI: 10.1002/sim.7223. View

12.

McHugh M . Interrater reliability: the kappa statistic. Biochem Med (Zagreb). 2012; 22(3):276-82. PMC: 3900052. View

13.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

14.

Turroni S, Brigidi P, Cavalli A, Candela M . Microbiota-Host Transgenomic Metabolism, Bioactive Molecules from the Inside. J Med Chem. 2017; 61(1):47-61. DOI: 10.1021/acs.jmedchem.7b00244. View

15.

Wei J, Yang Z, Li J, Zhang Y, Zhang W, Doherty M . Association between gut microbiome-related metabolites and symptomatic hand osteoarthritis in two independent cohorts. EBioMedicine. 2023; 98:104892. PMC: 10775900. DOI: 10.1016/j.ebiom.2023.104892. View

16.

Rover C, Bender R, Dias S, Schmid C, Schmidli H, Sturtz S . On weakly informative prior distributions for the heterogeneity parameter in Bayesian random-effects meta-analysis. Res Synth Methods. 2021; 12(4):448-474. DOI: 10.1002/jrsm.1475. View

17.

Woodell-May J, Sommerfeld S . Role of Inflammation and the Immune System in the Progression of Osteoarthritis. J Orthop Res. 2019; 38(2):253-257. DOI: 10.1002/jor.24457. View

18.

Abeltino A, Hatem D, Serantoni C, Riente A, Giulio M, De Spirito M . Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine. Nutrients. 2024; 16(22). PMC: 11597134. DOI: 10.3390/nu16223806. View

19.

Gaspar M, Nunez-Carro C, Blanco-Blanco M, Blanco F, de Andres M . Inflammaging contributes to osteoarthritis development and human microbiota variations and vice versa: A systematic review. Osteoarthritis Cartilage. 2024; 33(2):218-230. DOI: 10.1016/j.joca.2024.11.005. View